Fosamprenavir Calcium Salt

Base Information

• Chemical Name: Fosamprenavir Calcium Salt
• CAS No.: 226700-81-8
• Molecular Formula: C25H34CaN3O9PS
• Molecular Weight: 623.67
• European Community (EC) Number: 607-123-4
• Mol file: 226700-81-8.mol

Synonyms:Fosamprenavir Calcium Salt;226700-81-8;SCHEMBL292385;s6581

Chemical Property of Fosamprenavir Calcium Salt

Chemical Property:

• Appearance/Colour: white microcrystalline needles
• Melting Point: 282-284 °C
• PSA: 201.57000
• LogP: 5.44910
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility.: Aqueous Acid (Slightly), DMF (Slightly)
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 14
• Exact Mass: 625.1535788
• Heavy Atom Count: 40
• Complexity: 912

Purity/Quality:

99% ^*data from raw suppliers

Fosamprenavir Calcium Salt ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)CN(CC(C(CC1=CC=CC=C1)NC(=O)OC2CCOC2)OP(=O)(O)O)S(=O)(=O)C3=CC=C(C=C3)N.[Ca]
• Isomeric SMILES: CC(C)CN(C[C@H]([C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CCOC2)OP(=O)(O)O)S(=O)(=O)C3=CC=C(C=C3)N.[Ca]
• Recent EU Clinical Trials: Impact of stomach motility on the gastrointestinal behavior of fosamprenavir in healthy volunteers
• Description: Fosamprenavir, a prodrug of the HIV protease inhibitor amprenavir, is indicated for the oral treatment of HIV infection in adults in combination with other antiretroviral agents. Although amprenavir has excellent antiviral potency and good tolerability, its watersolubility is poor (0.04 mg/ml). As a result, the formulation of the agent includes a high percentage of organic excipients to facilitate gastric dissolution, which limits the amount of active drug that can be formulated per capsule. Fosamprenavir is a highly soluble phosphate ester of amprenavir. It allows more convenient dosing and reduction in pill counts as compared to amprenavir. Fosamprenavir is readily prepared in two steps starting from a key intermediate used in the synthesis of amprenavir, by phosphorylating a hydroxyl group and subsequently reducing a p-nitrophenyl to a p-aminophenyl group. Fosamprenavir has little or no antiviral activity in vitro. After oral administration, it is rapidly and almost completely hydrolyzed by phosphatases in the gut epithelium to amprenavir prior to reaching systemic circulation. The time to reach peak plasma concentration of amprenavir is approximately 2.5 h and the plasma elimination half-life is approximately 7.7 h. Amprenavir is metabolized in the liver by CYP3A4 and ＞90% of the dose is excreted as metabolites in urine and feces. In most patients, fosamprenavir is administered at daily doses of 700–1400 mg in conjunction with ritonavir. Monotherapy with fosamprenavir is only recommended in antiretroviral therapy-na?ve patients and the dosing regimen is 1400 mg twice daily. The most common adverse events experienced with fosamprenavir are diarrhea, nausea, vomiting, headache and rash. Fosamprenavir (calcium salt) is an orally bioavailable prodrug of the HIV-1 protease inhibitor amprenavir . Fosamprenavir has improved solubility compared with amprenavir, and its pharmacokinetics, either during fasting or with a low- or high-fat meal, suggest that it could be effective using fewer tablets and a less complex dosing schedule than other HIV treatments. Formulations containing fosamprenavir are used for adult and pediatric patients with HIV infection, especially as an initial antiretroviral therapy.
• Uses: HIV protease inhibitor; water soluble prodrug of amprenavir HIV protease inhibitor; water soluble prodrug of amprenavir.
• Clinical Use: Fosamprenavir calcium has been approved for the treatment of HIV in adults when used in combination with other anti-HIV drugs. It is a prodrug that, on hydrolysis by serum phosphatases, gives rise to amprenavir, which is a peptidomimetic transition-state inhibitor that targets HIV-1 protease and reduces the viral replication and, thus, the infectiousness of HIV-1. It is commonly administered in combination with RT inhibitors to produce excellent efficacy in patients with AIDS. The drug is administered as two 700 mg tablets twice daily or, in combination with ritonavir, can be given as two 700 mg tables once daily or one 700 mg tablet twice daily. As a result, formaprenavir lowers the "pill burden" in patients with AIDS.
• Drug interactions: Potentially hazardous interactions with other drugs Anti-arrhythmics: possibly increased concentration of amiodarone, flecainide, lidocaine and propafenone (increased risk of ventricular arrhythmias) - avoid. Antibacterials: increases concentration of rifabutin - reduce rifabutin dose; concentration significantly reduced by rifampicin - avoid; avoid with telithromycin in severe renal and hepatic impairment. Anticoagulants: avoid with apixaban and rivaroxaban. Antidepressants: concentration reduced by St John’s wort - avoid. Antimalarials: use artemether/lumefantrine with caution; possibly increases quinine concentration. Antipsychotics: possibly inhibits aripiprazole metabolism - reduce aripiprazole dose; possibly increases quetiapine concentration - avoid; possibly increases pimozide concentration (increased risk of ventricular arrhythmias) - avoid. Antivirals: avoid with boceprevir, raltegravir and telaprevir; concentration of dolutegravir reduced; concentration increased by etravirine, consider reducing fosamprenavir dose; concentration reduced by lopinavir, maraviroc and tipranavir, effect on lopinavir unpredictable - avoid, avoid with maraviroc; concentration possibly reduced by nevirapine; avoid with raltegravir. Anxiolytics and hypnotics: increased risk of prolonged sedation and respiratory depression with midazolam - avoid with oral midazolam. Avanafil: concentration of avanafil possibly increased. Cytotoxics: possibly increases concentration of bosutinib and ibrutinib, avoid or consider reducing bosutinib and ibrutinib dose. Ergot alkaloids: increased risk of ergotism - avoid. Immunosuppressants: monitor ciclosporin, tacrolimus and sirolimus levels. Lomitapide: avoid concomitant use. Orlistat: absorption possibly reduced by orlistat. Ranolazine: possibly increases ranolazine concentration - avoid. Statins: possibly increased risk of myopathy with atorvastatin; possibly increased myopathy with simvastatin and rosuvastatin - avoid.